1. Field of the Invention
This invention relates to devices and methods for the co-culturing of cells and more specifically to an insert device or tray that when assembled with a well or multi-well plate forms a co-culture device assembly having upper and lower chambers separated by a microporous membrane or barrier and method of use for the growing and/or assaying of biological cells.
2. Description of the Related Art
Various inserts having a porous bottom membrane for use with microtiter plates have been developed and are in use throughout the biological science community as dual chamber cell culture systems. Such systems are commonly used to culture or grow two types of cells in an indirect co-culture environment with one cell type growing in an upper chamber and another in a lower chamber. One such use is to assess the potential relationship between “effector” cells and “target” cells. Specifically, effector cells may secrete molecules which may act on target cells, causing different biological effects such as, promoting the growth of target cells, causing cytotoxic effects on target cells, or activating specific receptors or other molecular targets on the target cells. Thus, the combination of the insert and the microtiter plate is useful to examine the indirect interactions between two different cell lines or cell types, such as paracrine signaling affecting cell proliferation, cell survival and cytotoxicity effect. This paracrine signaling effect can be assayed by readouts such as end-point assay readouts (e.g. MTT based assays using plate reader and imaging based readout) in regular micro-titer plates. Examples of such devices have been described in a number of US patents, including U.S. Pat. No. 5,026,649; U.S. Pat. No. 4,871,674; U.S. Pat. No. 5,366,893; U.S. Pat. No. 5,534,227; U.S. Pat. No. 5,801,055; U.S. Pat. No. 5,665,596; U.S. Pat. No. 5,583,037. Current approaches typically suffer from one or more challenges. Among these include challenges associated with movement of the insert within the multi-well plate when accessing the lower chamber, potential contamination from the upper chamber when accessing the lower chamber and the addition of complex features or mechanisms to reduce movement of the upper chamber. Further, some configurations are labor intensive and reveal only limited information at a single time point. Accordingly, there remains a need to develop new devices, systems and methods that reduce chamber movement, reduce potential sample contamination, are simple to operate and offer a variety of information across multiple time points.